Abstract
The structural preferences of the pH-sensitive phospholipid, N- succinyldioleoylphosphatidylethanolamine ( N- succinyl-DOPE ), have been examined alone and in mixtures with DOPE by 31P-NMR, fluorescence energy transfer, and freeze-fracture techniques. The basic polymorphic behavior of pure N- succinyl-DOPE and DOPE/N- succinyl-DOPE lipid systems and the influence of calcium and pH were investigated. It is shown that, similar to other negatively charged acidic phospholipids, N- succinyl-DOPE adopts the bilayer organization upon hydration. This structure is maintained at both pH 7.4 and 4.0 in the presence or absence of calcium. In the mixed lipid system, N- succinyl-DOPE can stabilize the non-bilayer lipid, DOPE, into a bilayer structure at both pH 7.4 and 4.0 at more than 10 mol% N- succinyl-DOPE , although a narrow 31P-NMR lineshape is observed at acidic pH values. This corresponds to the presence of smaller vesicles as shown by quasi-elastic light scattering measurements. Addition of equimolar calcium (with respect to N- succinyl-DOPE ) to the DOPE/N- succinyl-DOPE systems induces the hexagonal H II phase at both pH values. In unilamellar systems with similar lipid composition the addition of Ca 2+ results in membrane fusion as indicated by fluorescence energy-transfer experiments. These findings are discussed with regard to the molecular mechanism of the bilayer to hexagonal H II phase transition and membrane fusion and the utility of N- succinyl-DOPE containing pH-sensitive vesicles as drug-delivery vehicles.
Published Version
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